DoD Combat Readiness - Translational Research Award

The CRRP seeks to increase pre-hospital survivability of the Warfighter by enabling individuals, of varying expertise, to address casualties of the battlespace and closer to the point of injury. The intent of the FY23 CRRP TRA is to support high-impact translational research that will accelerate innovative ideas into clinical applications, including health care products, technologies, and/or practice guidelines. Research funded under this award mechanism will be hypothesis-driven, high-impact applied research that is relevant to active-duty Service Members, Veterans, other military beneficiaries, and the American public.

Applicants may leverage existing resources in translational research to address high-impact research ideas or unmet needs to enable the delivery of life-saving care to the Warfighter during prolonged and en route care in austere and combat environments. For this award mechanism, the definition of “leveraging” is as follows: An investigator basing a research project on existing resources in order to amplify potential gains in knowledge or accelerate technical maturity. Research of interest may include knowledge products, “knowledge resulting from research with the potential to improve individual or public health,”2 and solutions that can accelerate the introduction of military-relevant health products or technologies into clinical and/or operational use. Projects should take into consideration the varied expertise levels of targeted medical providers, available resources, and the possible diverse environmental conditions in combat situations. Proposal/application submissions are encouraged to include characteristics relevant to military use in the pre-hospital, combat operational setting. Submissions that propose solutions to advance civilian trauma care are not precluded, since civilian trauma and trauma care in the military are mutually influential and may be co-occurring in certain situations.

Impact is a key component of this award mechanism. The potential impact of the research, both short term and long term, in addressing the FY23 CRRP Focus Area(s) should be clearly described. Successful high-impact research should lead to the rapid development and translation of applicable advances for improving medical readiness, mitigating fatalities, optimally treating life-threatening injuries, and promoting positive long-term outcomes for military health and medicine, as well as the general public.

Key aspects of the CRRP Translational Research Award Mechanism:

• This BAA may be used to support applied, preclinical, and/or clinical research.

• Clinical trials for U.S. Food and Drug Administration (FDA) licensure of drugs and definitive/pivotal testing for device clearance by the FDA will NOT be permitted under this BAA.

• Preliminary data are required: Inclusion of preliminary data relevant to the proposed study is required.

• Statistical Analysis and Data Management Plans: The application should include a clearly articulated statistical analysis plan; a power analysis reflecting sample size projections that will answer the objectives of the study; and a data management plan and use of an appropriate database to safeguard and maintain the integrity of the data.

Applications in response to this BAA may not be used to support fundamental basic research. For this BAA, basic research is defined as research directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications toward process or products in mind. Applied and preclinical research, including animal studies, that is already supported by substantial preliminary or published data, and is designed to validate clinical translation, is appropriate for this award mechanism.

Funding from this BAA may not be used to support studies requiring an exception from informed consent (EFIC).

Clinical research encompasses research with patient samples, data, and interaction with patients that may or may not be considered a clinical trial. For the purposes of this funding opportunity, research that meets the definition of a clinical trial is distinct from clinical research. Clinical research is observational in nature and includes: (1) Research that does not seek to evaluate the effects of interventions. Research conducted with human subjects (or on material of human origin such as data, tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects, but does not seek to assess the effects of an intervention, qualifies as clinical research. Patient-oriented research may include but is not limited to: (a) mechanisms of human disease, (b) diagnostic or detection studies (e.g., biomarker or imaging), (c) health disparity studies, and (d) development of new technologies. (2) Epidemiologic and behavioral studies that do not seek to study the safety, effectiveness, and/or efficacy outcomes of an intervention. (3) Outcomes research and health services research that do not fit under the definition of clinical trial. Excluded from the definition of clinical research are in vitro studies that utilize human tissues that cannot be linked to a living individual. Note: Studies that meet the requirements for exemption under §46.104(d)(4) of the Common Rule are not considered clinical research as defined by CDMRP. Exemption category 4 refers to secondary research for which consent is not required.

A clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or another control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. Clinical trials are not allowed under this funding opportunity announcement.

Studies that do not seek to measure safety, effectiveness, and/or efficacy outcome(s) of an intervention are not considered clinical trials.

The period of performance of the CRRP TRA will be 2 years. The anticipated total costs budgeted for an FY23 CRRP TRA should not exceed $1.1M.

Refer to Section II.D.6, Funding Restrictions, for detailed funding information.

Awards will be made no later than September 30, 2024. For additional information refer to Section II.F.1, Federal Award Notices.

The CDMRP expects to allot approximately $4.4M to fund approximately four CRRP Translational Research Award proposals/applications. Funding of proposals/applications received is contingent upon the availability of federal funds for this program as well as the number of proposals/applications received, the quality and merit of the proposals/applications as evaluated by scientific and programmatic review, and the requirements of the government. Funds to be obligated on any award resulting from this funding opportunity will be available for use for a limited time period based on the fiscal year of the funds. It is anticipated that awards made from this FY23 funding opportunity will be funded with FY23 funds, which will expire for use on September 30, 2029.

Proposals/applications received in response to both the extramural FY23 CRRP TRA BAA and the intramural program announcement will be evaluated and considered for funding. The government reserves the right to fund any combination of extramural and/or intramural proposals/applications.

The USAMRDC executes its extramural research program primarily through the awarding of contracts, assistance agreements (grants and cooperative agreements), and Other Transaction Agreements (OTAs). The type of instrument used to reflect the business relationship between the organization and the government is at the discretion of the government, in accordance with the Federal Grant and Cooperative Agreement Act of 1977, as amended, 31 USC 6301-6308, which provides the legal criteria to select a procurement contract or an assistance agreement.

An assistance agreement (grant or cooperative agreement) is appropriate when the federal government transfers a “thing of value” to a “state, local government,” or “other recipient” to carry out a public purpose of support or stimulation authorized by a law of the United States, instead of acquiring property or service for the direct benefit and use of the U.S. government. An assistance agreement can take the form of a grant or cooperative agreement. If “no substantial involvement” on the part of the funding agency is anticipated, a grant award will be made (31 USC 6304).

Conversely, if substantial involvement on the part of the funding agency is anticipated, a cooperative agreement will be made (31 USC 6305) and the award will identify the specific substantial involvement. Substantial involvement may include collaboration, participation, or intervention in the research to be performed under the award.

A contract is required when the principal purpose of the instrument is to acquire property or services for the direct benefit or use of the U.S. government.

An Other Transaction (OT) will also be considered as a vehicle for award under this BAA, in accordance with 10 USC 4021 and 10 USC 4022. The OT authorities were created to give the DOD the flexibility necessary to adopt and incorporate business practices that reflect commercial industry standards and best practices into its award instruments. When leveraged appropriately, OTs provide the government with access to state-of-the-art technology solutions from traditional and non-traditional defense contractors (NDCs), through a multitude of potential teaming arrangements tailored to the particular project and the needs of the participants. OTs can help to foster new relationships and practices involving traditional and NDCs, especially those that may not be interested in entering into FAR-based contracts with the government; broaden the industrial base available to government; support dual-use projects; encourage flexible, quicker, and cheaper project design and execution; leverage commercial industry investment in technology development and partner with industry to ensure DOD requirements are incorporated into future technologies and products; and collaborate in innovative arrangements. OTs are not FAR-based procurement contracts, grants, cooperative agreements, or cooperative research and development agreements.

The award type, along with the start date, will be determined during the negotiation process.

Please see Appendix 2, Section E, of the General Submission Instructions for more information.

Research Involving Human Data, Human Anatomical Substances, Human Subjects, or Human Cadavers: All DOD-funded research involving new and ongoing research with human data, human anatomical substances, human subjects, or human cadavers must be reviewed and approved by the USAMRDC Office of Human and Animal Research Oversight (OHARO), Office of Human Research Oversight (OHRO), prior to research implementation. This administrative review requirement is in addition to the local Institutional Review Board (IRB) or Ethics Committee (EC) review. Local IRB/EC approval at the time of application submission is not required; however local IRB/EC approval is necessary prior to OHRO review. Allow up to 3 months to complete the OHRO regulatory review and approval process following submission of all required and complete documents to the OHRO. Refer to the General Submission Instructions, Appendix 1, and the OHARO web page https://mrdc.health.mil/index.cfm/collaborate/research_protections/hrpo for additional information.

As of January 20, 2020, U.S. institutions engaged in non-exempt cooperative research must rely on a single IRB to review and approve the portion of the research conducted at domestic sites in accordance with Code of Federal Regulations, Title 45, Part 46.114(b) (45 CFR 46.114[b]). If the proposed, non-exempt research involves more than one U.S.-based institution, a written plan for single IRB review arrangements must be provided at the time of application submission or award negotiation. The lead institution responsible for developing the master protocol and master consent form should be identified and should be the single point of contact for regulatory submissions and requirements.

Rigor of Experimental Design: All projects should adhere to accepted standards for rigorous study design and reporting to maximize the reproducibility and translational potential of preclinical research. The standards are described in SC Landis et al., 2012, A call for transparent reporting to optimize the predictive value of preclinical research, Nature 490:187-191 (https://www.nature.com/articles/nature11556). While these standards are written for preclinical studies, the basic principles of randomization, blinding, sample-size estimation, and data handling derive from well-established best practices in clinical studies. Projects that include research on animal models are required to submit Attachment 8, Animal Research Plan, as part of the application package to describe how these standards will be addressed. Applicants should consult the ARRIVE guidelines 2.0 (Animal Research: Reporting In Vivo Experiments) to ensure relevant aspects of rigorous animal research are adequately planned for and, ultimately, reported. The ARRIVE guidelines 2.0 can be found at https://arriveguidelines.org/arrive-guidelines.

Use of DOD or Department of Veterans Affairs (VA) Resources: If the proposed research involves access to active-duty military and/or VA patient populations and/or DOD or VA resources or databases, the application must describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research. Refer to Section II.D.2.b.ii, Full Application Submission Components, for detailed information. Refer to the General Submission Instructions, Appendix 1, for additional information.

Research Involving Animals: All research funded by the FY23 CRRP TRA involving new and ongoing research with animals must be reviewed and approved by the USAMRDC OHARO Animal Care and Use Review Office (ACURO), in addition to the local Institutional Animal Care and Use Committee (IACUC) of record. IACUC approval at the time of submission is not required. Allow at least 3 to 4 months for ACURO regulatory review and approval processes for animal studies. Refer to the General Submission Instructions, Appendix 1, for additional information.

The CDMRP intends that information, data, and research resources generated under awards funded by this BAA be made available to the research community (which includes both scientific and consumer advocacy communities) and to the public at large. For additional guidance, refer to the General Submission Instructions, Appendix 2, Section L.

Federal Interagency Traumatic Brain Injury Research (FITBIR) Data Sharing: The DOD requires that awardees make any traumatic brain injury (TBI) focused research data generated by this award mechanism available to the research community through the FITBIR Informatics System. The FITBIR Informatics System is a free resource designed to accelerate research progress by allowing the storage, reanalysis, integration, and rigorous comparison of multiple datasets. Currently, FITBIR-eligible research includes all studies generating prospectively collected human TBI subject data (e.g., clinical, demographic, phenotypic, imaging and genetic). Consult the FITBIR website at https://fitbir.nih.gov for additional information. Elements that must be included in the proposed research can be found in Appendix IV.